Is MAP3K14 p.Ser549= (c.1647C>T) pathogenic?

MAP3K14 p.Ser549= (c.1647C>T) is classified Likely benign in MAP3K14 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-12-20). Absent from gnomAD v4.1; Associated with MAP3K14-related disorder.

What condition is associated with MAP3K14 p.Ser549= (c.1647C>T)?

MAP3K14 p.Ser549= (c.1647C>T) is associated with MAP3K14-related disorder (ClinVar).

How common is MAP3K14 p.Ser549= (c.1647C>T) in the general population?

MAP3K14 p.Ser549= (c.1647C>T) is absent from gnomAD v4.1 (gnomAD).

MAP3K14 p.Ser549=

c.1647C>T · rs2044155646 · VCV3061708

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

MAP3K14-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.9	GERP -0.39, phastCons 0.97
Overall
CADD	7.781	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MAP3K14
Protein: p.Ser549=
Coding: c.1647C>T
MANE Select: NM_003954
dbSNP: rs2044155646
Type: single nucleotide variant
Location: chr17:45273513 (GRCh38)
Gene constraint: LOEUF 0.263 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 61.00 · 8 PDB
Residue 549: the protein kinase domain; the 'interaction with zfp91' region

Full MAP3K14 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

MAP3K14-related disorder

Similar variants

MAP3K14 p.Ile630Met Likely benign ★ same condition
MAP3K14 p.Tyr336= Likely benign ★ same condition
MAP3K14 p.Ala103Thr Uncertain significance ★★ ⚠ same type
MAP3K14 p.Ala142Ser Uncertain significance ★★ ⚠ same type
MAP3K14 p.Ala575Thr Uncertain significance ★★ ⚠ same type
MAP3K14 p.Arg131His Uncertain significance ★★ ⚠ same type
MAP3K14 p.Arg146Gln Uncertain significance ★★ ⚠ same type
MAP3K14 p.Arg218Gln Uncertain significance ★★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/map3k14-p-ser549 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown